Kimmo Luomanmäki

Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial

BACKGROUND Angiotensin-converting-enzyme (ACE) inhibitors have been used for more than a decade to treat high blood pressure, despite the lack of data from randomised intervention trials to show that such treatment affects cardiovascular morbidity and mortality. The Captopril Prevention Project (CAPPP) is a randomised intervention trial to compare the effects of ACE inhibition and conventional therapy on cardiovascular morbidity and mortality in patients with hypertension. METHODS CAPPP was a prospective, randomised, open trial with blinded endpoint evaluation. 10,985 patients were enrolled at 536 health centres in Sweden and Finland. Patients aged 25-66 years with a measured diastolic blood pressure of 100 mm Hg or more on two occasions were randomly assigned captopril or conventional antihypertensive treatment (diuretics, beta-blockers). Analysis was by intention-to-treat. The primary endpoint was a composite of fatal and non-fatal myocardial infarction, stroke, and other cardiovascular deaths. FINDINGS Of 5492 patients assigned captopril and 5493 assigned conventional therapy, 14 and 13, respectively, were lost to follow-up. Primary endpoint events occurred in 363 patients in the captopril group (11.1 per 1000 patient-years) and 335 in the conventional-treatment group (10.2 per 1000 patient-years; relative risk 1.05 [95% CI 0.90-1.22], p=0-52). Cardiovascular mortality was lower with captopril than with conventional treatment (76 vs 95 events; relative risk 0.77 [0.57-1-04], p=0.092), the rate of fatal and non-fatal myocardial infarction was similar (162 vs 161), but fatal and non-fatal stroke was more common with captopril (189 vs 148; 1.25 [1-01-1-55]. p=0.044). INTERPRETATION Captopril and conventional treatment did not differ in efficacy in preventing cardiovascular morbidity and mortality. The difference in stroke risk is probably due to the lower levels of blood pressure obtained initially in previously treated patients randomised to conventional therapy.

A prospective study of acute poisonings in Finnish hospital patients.

1 We have carried out a prospective study of all adult patients presenting with acute poisoning during one month to the Helsinki University Central Hospital (Meilahti Hospital). 2 Two hundred and twenty-six cases of acute poisoning (113 males and 113 females) presented to the emergency department. Most cases in both men (66%) and women (67%) involved alcohol. As to drugs, psychotropic agents predominated in both men and women. The frequency of patient presentation peaked between 7 p.m. and 9 p.m. and was lowest between 8 a.m. and 10 a.m. In most cases, the delay from ingestion of the poison to presentation was longer than 4h. 3 The clinical status of the patients on arrival was generally good; more than half (55%) of them were fully awake. Serious symptoms (e.g. unconsciousness, insufficient respiration necessitating intubation, aspiration, convulsions or hypotension) occurred in 15% of the presentations. There were no fatalities. 4 One hundred and thirty-five patients (60%) received at least one 50-g dose of activated charcoal. However, charcoal was given in 86% of the cases of drug poisoning. Gastric lavage was performed in 112 cases (50%), and 106 cases (47%) involved both gastric lavage and administration of charcoal. Twenty-one patients received antidotes (flumazenil, calcium gluconate or naloxone) and three patients were hemodialysed. 5 Of the 226 cases, 142 (63%) were managed solely in the emergency department. Of the 84 cases admitted to the hospital, eight had to be managed in the intensive care unit. Almost all patients (94%) were discharged within 24 h. 6 In this survey on 226 consecutive cases of acute poisoning, about two-thirds of the cases involved alcohol, while the most common drugs taken were psychotropic agents. The poisoning was mild in the great majority of the cases. Activated charcoal was generally administered in all but trivial cases of drug poisoning.

Syncope and Q-T prolongation without deafness: The Romano-Ward syndrome

Abstract A case of the Romano-Ward syndrome in a 26-year-old woman is reported. The patient presented on account of recurrent ep sodes of syncope. The electrocardiogram showed a grossly abnormal T-U-wave complex producing apparent great prolongation of the Q-T interval. This was mostly due to fusion of the abnormally prominent U wave with the T wave. Hemodynamic studies showed normal structure and function of the heart, which, however, was exceptionally liable to develop ventricular tachycardia and fibrillation.

Serial Observations on Left Ventricular Dysfunction in Acute Myocardial Infarction II. Systolic Time Intervals in Power Failure

Systolic time intervals corrected for heart rate were studied serially in 50 patients with acute myocardial infarction (AMI) 1, 5, and 20 days after the onset of symptoms from simultaneously recorded kineto-, phono-, and electrocardiograms and carotid artery pulse tracings. Left ventricular ejection time (LVET), electromechanical systole (QA2), and mechanical systole (M1A2) decreased from the first to the fifth day (P < 0.001) and increased again toward normal by the twentieth day. There was a clear correlation with the clinically assessed severity of AMI; the high prevalence of abnormal values indicated a frequent and early impairment of left ventricular performance. In severe power failure, deterioration was indicated by progressive shortening of the systolic time intervals, as contrasted to gradual improvement noted in uncomplicated infarctions. Similarly, LVET, QA2, and M1A2 displayed a significant correlation with the grade of radiologically assessed pulmonary vascular congestion on the first day. A relationship between LVET, QA2, and isovolumic contraction time (ICT)/LVET and the degree of paradoxical cardiac pulsation became apparent on the fifth day. LVET, M1A2, ICT/LVET, and preejection period (PEP)/LVET were more abnormal in the nine patients who died than in the 41 survivors (P < 0.05). PEP and ICT showed no correlation with clinically or radiologically assessed severity or prognosis of infarction, in contrast to findings in chronic heart failure. Decrease of contractility in AMI appears not to be directly reflected in preejection intervals. These findings indicate the value of externally measured left ventricular systolic time intervals, especially LVET, in assessment of the severity and prognosis of AMI.

The Captopril Prevention Project (CAPPP) in Hypertension—Baseline Data and Current Status

The Captopril Prevention Project (CAPPP) is an ongoing intervention study conducted in 11,019 hypertensive patients in Sweden and Finland. Patients have been randomized to receive either conventional antihypertensive therapy (diuretics and/or beta-blockers) or captopril-based treatment. A prospective, randomized, open, blinded-endpoint evaluation (PROBE) study design is used to compare these two therapeutic regimens as regards cardiovascular morbidity and mortality. The rationale for the CAPPP Study are the many observations of beneficial effects of ACE inhibition, as compared to diuretics and beta-blockers, on intermediary endpoints such as insulin sensitivity, serum lipoproteins, left ventricular hypertrophy and renal function. Captopril has also been shown to be markedly effective in the treatment of left ventricular dysfunction as well as congestive heart failure. The hypothesis is that these differences might result in improved risk reduction when ACE inhibitors are used in the treatment of hypertension. The present paper describes the baseline data and the changes in blood pressure during the first year in the total cohort. During the first year the average blood pressure was reduced by 11/8 mm Hg. A number of substudies have been conducted in the CAPPP Study. In one of these insulin sensitivity was compared in a subgroup of the patients using the euglycemic insulin clamp technique. In another substudy the ACE gene was sequenced and some new polymorphisms were discovered. Several other substudies are in progress or in the planning phase. The main results of the CAPPP Study should be available by mid-1998. Some of the intended anayses of the final results as well as other planned substudies are briefly described here.

Value of serial P wave changes in indicating left heart failure in myocardial infarction.

In order to evaluate ventricular failure in acute myocardial infarction, electrocardiographic left atrial overloading was correlated to several simultaneous clinical and radiological signs of left ventricular dysfunction in 200 consecutive patients. Analyses were made at three time periods after infarction. Left atrial overloading, measured by P terminal force, was significantly associated with the signs of left ventricular dysfunction, though in this unselected series of infarctions the prevalence of abnormal values was not high (46%). This finding is to be considered rather as a contributory sign than as a diagnostic one in the entire clinical picture. In an individual patient, however, conspicuous serial changes are helpful in indicating the direction of course of the haemodynamic disorder. The prognostic value of the P terminal force was found to be significant.

Pharmacokinetics of diltiazem in massive overdose.

Several cases of poisoning with diltiazem have been described in the literature, but information about the pharmacokinetics of diltiazem in overdose is sparse. The authors report pharmacokinetic and clinical observations in a patient who ingested 7.2 g of slow-release dilitiazem. Grave, persistent hypotension was the overriding clinical manifestation, but the patient eventually survived with aggressive cardiovascular support. No serious conduction abnormalities were seen. Blood samples were taken repeatedly for 2-3 days for analysis of serum diltiazem and desacetyldiltiazem and desacetyldiltiazem concentrations. The serum diltiazem concentration measured in the first sample taken (16.5 h postingestion), 3,171 ng/ml, is one of the highest concentrations reported in a patient who survived. The half-life was 13.3 h for diltiazem and 10.5 h for desacetyldiltiazem. Charcoal hemoperfusion had no apparent effect on the elimination of either compound. The relatively long half-life of diltiazem may have resulted from rate-limiting absorption and probably does not indicate saturation of diltiazem metabolism. The patient was discharged with no apparent neurological or cardiological deficits.

Isolated Pericardial Rupture After Blunt Chest Injury

A case of isolated pericardial defect, probably due to blunt chest injury, in a symptomless 39-year-old man is described. The diagnosis was based on the clinical finding of an abnormal paradoxic pulsation at the 3rd intercostal space in the absence of auscultatory abnormalities or ischaemic heart disease, and on the characteristic shape of the heart in the plain chest radiograph. Artificial pneumothorax and cardioangiography confirmed the diagnosis.